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A Nose for Disease

In 1989, The Lancet carried a curious report on a dog that kept licking a mole on her owner's leg. The mole turned out to be a malignant melanoma. Since then, scientists have observed similar "disease sniffing" abilities in mice and rats, which tend to avoid sickly members of their own species. Now researchers think they have figured out how these animals do it.

Scientists have previously identified a number of mouse smell receptors, cell-surface proteins in the animals' noses that pick up everything from the fragrance of food to the scent of fear (ScienceNOW, 21 August 2008). Neurogeneticist Ivan Rodriguez of the University of Geneva in Switzerland and colleagues wondered whether there might be additional such receptors that respond to a disease "scent," perhaps by detecting chemicals associated with bacteria and inflammation.

The researchers scoured the already deciphered mouse genome, looking for genes that might encode additional receptor proteins in its olfactory system, the sensory cells that connect the nose to the brain. They found genes for five new receptors, all of which belong to a known family of proteins called formyl peptide receptors (FPRs).

The known FPRs include two immune system receptors that detect chemicals given off by pathogens in the blood, helping immune cells track down and attack foreign bodies. Could the newly identified ones on olfactory cells do the same, detecting pathogens but those outside the body on another animal? Rodriguez's team exposed olfactory mouse neurons in the lab to disease-causing bacteria and the urine of sick mice. Sure enough, some of the chemicals sparked a "smell response" in the neurons, as reflected by electrical changes in the cells, the researchers report online today in Nature.

The neurons possessing the newfound FPR receptors reside within a part of the olfactory system at the base of the brain that also sniffs out sexual signaling chemicals called pheromones. This area--the vomeronasal organ--is linked directly to the brain's emotional center, the amygdala. "This makes a lot of sense," says Rodriguez. When a mouse detects a nearby mate, or danger, in the form of disease, it needs to trigger a quick reaction, whether it's an attempt to reproduce or to avoid a nearby sick animal, he says.

Rodriguez's team also found disease-smelling receptors in gerbils and rats, but he thinks it's unlikely they'll be discovered in human noses. There's no evidence that we have FPRs anywhere but in our immune system, he says.

The results are "very exciting, if not a major breakthrough," says neuroscientist and smell expert Pierre Marie Lledo of the Pasteur Institute in Paris. The discovery will open "new field of research" into the molecular basis of sniffing out disease, says Marie-Christine Broillet, a specialist in olfaction from the University of Lausanne in Switzerland.